E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027105 |
E.1.2 | Term | Medullary thyroid cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate an improvement in progression-free survival (PFS) with ZD6474 as compared to placebo in subjects with unresectable locally advanced or metastatic MTC |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate an improvement in the overall objective response rate (ORR), disease control rate (DCR), and duration of response (DOR) with ZD6474 as compared to placebo
2. To demonstrate an improvement in the overall survival (OS) in subjects with MTC who have been treated with ZD6474 as compared to placebo
3. To demonstrate an improvement in biochemical response with ZD6474 as compared to placebo as measured by calcitonin (CTN) and carcinoembryonic antigen (CEA)
4. To demonstrate a delay in time to worsening of pain (TWP) among subjects with MTC after treatment with ZD6474 as compared to placebo
5. To determine the pharmacokinetics (PK) of ZD6474 in this subject population and investigate any influence of subject demography and pathophysiology on the PK
PLUS other secondary and exploratory objectives as detailed in the protocol |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic MTC.
Presence of a measurable tumour
Able to swallow medication
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E.4 | Principal exclusion criteria |
Major surgery within 4 weeks before randomisation
The last dose of prior chemotherapy received less than 4 weeks prior to randomization
Radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy)
Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days
Significant cardiac event
Previous ZD6474 treatment
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time to progression or death |
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E.5.2 | Secondary end point(s) |
1. Objective Response Rate by RECIST, Disease Control Rate and Duration of Response
2. Overall Survival
3. CTN and CEA
4. Time to Worsening of Pain
5. Incidence and type of AEs, clinically significant laboratory abnormalities, ECG changes and vital signs
6. Other PK variables
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See protocol study plan for detailed information regarding the timing of these evaluations |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Brazil |
Canada |
India |
Korea, Republic of |
Mexico |
Russian Federation |
Serbia |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Subjects who continue to receive ZD6474 study treatment will receive open label supplies for as long as the investigator determines they are obtaining clinical benefit, or until they are given another anti-cancer therapy other than the study medication.
However, where local regulations allow, subjects may be terminated from the study and switched from clinical supplies to marketed vandetanib in those territories where vandetanib is approved for the disease under study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 10 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |